BiostatisticsEpidemiological Studies

Jagdish Dukre

Epidemiological Studies

Observational studies

Analytical studies

Experimental studies

Observational studies

Cross sectional studies

Longitudinal studies

Cross sectional studiesSimplest form of observational studyGives distribution patterns which may suggest casual

hypothesisAlso known as prevalence studyTime sequence cannot be obtainedNo information about natural history and incidence of

disease

Bourne and colleagues conducted a cross sectional survey in Bangkok to estimate the burden of glaucoma.

They sampled and examined 701 people aged >50 years for glaucoma.

The estimated prevalence of glaucoma was 3.8%.

Longitudinal studiesObservations are repeated over the same population over

a period of time.

Time sequence can be studied

Gives information about natural history of disease and incidence rates

Also helps in identifying the risk factors of disease

Difficult to organize, expensive and more time consuming

Br J Ophthalmol 2012;96:811-815

In a population-based setting in adult Chinese, factors showing an association with open-angle glaucoma progression were a small rim and presence of disc haemorrhages.

Glaucoma progression was not significantly associated with optic disc size, central corneal thickness and systemic diseases such as diabetes mellitus and arterial hypertension.

Analytical studies

Case control studies

Cohort studies

Case control studiesCase-control studies are used to study the aetiology of

disease.

Case-control studies are conducted by recruiting Cases: people who have the disease of interest Controls : people without the disease

 Controls should be selected from the same population that gave rise to the cases

Cases and controls are interviewed or examined, to assess their exposure status.

The odds of exposure in cases and in controls is compared to assess the exposure-disease association.

Case-control studies are relatively quick and cheap to carry out.

They can also be used to investigate rare diseases and multiple exposures.

Recall bias is a problem, since cases may report exposures differently from controls.

There is also the potential for selection bias, particularly in the selection of the controls.

1844 controls were compared with 1844 patients with AMD.

The large case-control study suggests a relation between AMD and lens opacities.

Association between nuclear sclerosis and early stages of AMD, including drusen and RPE alterations, but no association with late stages of AMD.

Cohort studies

Cohort studies allow us to measure predictors of disease incidence.

To conduct a cohort study, a group of people free from the disease of interest are recruited and characterized as “exposed” or “unexposed” with respect to the risk factor under investigation.

The participants are followed over time and the number of incident cases of disease determined.

The incidence is calculated for the exposed and unexposed groups, and the incidence ratio is estimated.

Cohort studies can be Closed : where people are enrolled only at the beginning

of follow upOpen : where enrolment occurs over time.

The strengths of the cohort study design include the ability to measure the incidence of disease, several disease outcomes can be measured.

The main drawback is that large sample or long follow up is needed in cohort study.

This makes cohort studies expensive and time consuming.

Loss to follow up can leads to bias.

Six hundred thirty-nine subjects participated.Three hundred twenty-six of six hundred thirty-nine (51%)

subjects were traced and examined, 108 (17%) had died, and 205 (32%) were lost to follow-up.

Older age was a significant risk factor for development of trichiasis, corneal opacity, and visual loss .

Experimental studiesRandomised control trials (RCT) are most commonly used

for clinical studies.

Used to assess the benefit of a new drug or treatment, but they are also useful for evaluating the impact of a preventive measure (e.g. health education).

People are selected and randomized into the intervention or the control groups.

The purpose of randomization is to make the intervention and control groups as similar as possible.

The only difference between the groups is that one group receives the intervention while the other does not.

The two groups are monitored over time for the defined outcomes, allowing the relative risk to be calculated.

Randomization

Randomization is the process of assigning participantsto treatment and control groups, assuming that eachparticipant has an equal chance of being assigned to anygroup.

Randomization Techniques

Simple randomization,

Block randomization,

Stratified randomization, and

Covariate adaptive randomization

Simple RandomizationMaintains complete randomness of the assignment of

a person to a particular group.

Method of simple randomization is flipping a coin, a shuffled deck of cards or throwing a die.

Random number table or computer-generated random numbers can also be used

Simple randomization is easy to implement in a clinical trial.

In relatively small sample size clinical trials (n < 100), it results in an unequal number of participants among groups.

Block Randomization

The block randomization method is designed to randomize participants into groups that result in equal sample sizes.

The block size is determined by the researcher and should be a multiple of the number of groups.

After block size has been determined, all possible balanced combinations of assignment within the block must be calculated.

Blocks are then randomly chosen to determine the participants’ assignment into the groups.

Stratified Randomization

This method can be used to achieve balance among groups in terms of participants’ baseline characteristics (covariates).

Specific covariates must be identified by the researcher who understands the potential influence each covariate has on the dependent variable.

Stratified randomization is achieved by generating a separate block for each combination of covariates.

Participants then are assigned to the appropriate block of covariates.

After all participants have been identified and assigned into blocks, simple randomization occurs within each block to assign participants to one of the groups.

It useful technique, especially for smaller clinical trials.

It becomes complicated to implement if many covariates must be controlled.

It works only when all participants have been identified before group assignment.

Covariate Adaptive RandomizationA new participant is sequentially assigned to a particular

treatment group by taking into account the specific covariates and previous assignments of participants.

Various methods used are Taves methodFrane methodPocock and Simon method

Group assignment for the next participant can be readily predicted, going against the basic concept of randomization.

The computation process of covariate adaptive randomization is complicated, thereby limiting its use in practice.

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